Background
Methods
Trial design and participants
Baseline characteristics
Characteristics | (n) | Vitamin D + calcium | (n) | Placebo | (n) | Total cohort |
---|---|---|---|---|---|---|
Included men (%) | 151 | 49% | 156 | 51% | 307 | 100 |
Age (years) | 151 | 34 (30, 39) | 156 | 34 (31, 39) | 307 | 34 (30, 39) |
BMI (kg/m2) | 148 | 26 (24, 28) | 151 | 26 (24, 28) | 299 | 26 (24, 28) |
Current smokers (%) | 138 | 27% | 139 | 22% | 277 | 24% |
Cryptorchidism (%) | 142 | 14% | 140 | 16% | 282 | 15% |
Testis size (mL) | 136 | 19 (15, 23) | 133 | 18 (15, 21) | 269 | 18 (15, 22) |
Hormones | ||||||
AMH (pmol/L) | 147 | 33 (23, 50) | 151 | 32 (21, 55) | 298 | 33 (22, 54) |
Inhibin B (pg/mL) | 147 | 155 (109, 209) | 151 | 145 (99, 185) | 298 | 152 (106, 196) |
FSH (U/L) | 147 | 4.3 (2.6, 6.2) | 151 | 4.4 (2.9, 6.1) | 298 | 4.3 (2.7, 6.1) |
AMH/FSH ratio | 147 | 8 (4, 17) | 151 | 8 (4, 15) | 298 | 8 (4, 16) |
Inhibin B/FSH ratio | 147 | 40 (19, 76) | 151 | 36 (17, 60) | 298 | 37 (18, 67) |
LH (U/L) | 147 | 4.2 (3.1, 5.3) | 151 | 3.9 (2.8, 17.2) | 298 | 4.0 (2.9, 5.3) |
Testosterone (nmol/L) | 147 | 14 (11, 17) | 151 | 14 (11, 17) | 298 | 14 (11, 17) |
Testosterone/LH ratio | 147 | 3.3 (2.5, 4.9) | 151 | 3.6 (2.5, 5.2) | 298 | 3.5 (2.5, 5.0) |
Estradiol (pmol/L) | 147 | 96 (82, 113) | 151 | 99 (88, 117) | 298 | 98 (83, 116) |
Testosterone/Estradiol ratio | 147 | 149 (123, 185) | 151 | 136 (114, 182) | 298 | 145 (116, 183) |
25OHD (nmol/L) | 147 | 43 (29, 59) | 153 | 44 (29, 59) | 300 | 44 (29, 59) |
Semen parameters | ||||||
Abstinence (days) | 150 | 3.8 (3.0, 4.3) | 154 | 3.8 (3.0, 4.5) | 304 | 3.8 (3.0, 4.5) |
Semen volume (mL) | 150 | 3.8 (2.7, 5.0) | 156 | 3.6 (2.7, 4.5) | 306 | 3.6 (2.7, 4.7) |
Sperm concentration (106/mL) | 150 | 12 (4, 35) | 156 | 14 (3, 44) | 306 | 13 (4, 37) |
Sperm count (106) | 150 | 48 (15, 146) | 156 | 48 (10, 132) | 306 | 48 (14, 133) |
Motile sperm (%) | 144 | 41 (26, 58) | 149 | 48 (29, 63) | 293 | 45 (27, 61) |
Motile sperm (106) | 144 | 23 (5, 69) | 149 | 25 (4, 77) | 293 | 23 (5, 74) |
Progressive motile sperm (%) | 144 | 27 (15, 44) | 149 | 34 (17, 49) | 293 | 31 (16, 45) |
Progressive motile sperm (106) | 144 | 13 (3, 52) | 149 | 17 (3, 55) | 293 | 17 (3, 54) |
Morphological normal sperm (%) | 147 | 2.0 (0.8, 4.0) | 150 | 3.0 (1.5, 6.3) | 297 | 2.5 (1.0, 5.0) |
Morphological normal sperm (106) | 147 | 0.9 (0.2, 4.2) | 150 | 1.4 (0.1, 6.7) | 297 | 1.2 (0.2, 5.1) |
Biochemical analyses
Semen analyses
Statistical analyses
Results
Serum AMH and testicular function
AMH lowest tertile (n=100) | AMH median tertile (n=99) | AMH highest tertile (n=99) | *P-value | |
---|---|---|---|---|
Age (years) | 37 (32, 40) | 34 (30, 38) | 32 (29, 37) | <0.001 |
BMI (kg/m2) | 26 (24, 29) | 26 (23, 28) | 26 (23, 28) | 0.154 |
Smoking (%) | 27 (%) | 23 (%) | 24 (%) | 0.734 |
Cryptorchidism (%) | 18% | 15% | 13% | 0.715 |
Testis size (mL) | 17 (14, 20) | 19 (16, 22) | 20 (16, 25) | <0.001 |
AMH (pmol/L) | 17 (13, 22) | 33 (28, 39) | 64 (54, 78) | - |
Inhibin B (pg/mL) | 116 (82, 148) | 158 (117, 199) | 178 (140, 236) | <0.001 |
FSH (U/L) | 5.2 (3.7, 8.0) | 4.1 (2.9, 5.4) | 3.3 (2.2, 5.4) | <0.001 |
AMH/FSH ratio | 3.4 (2.0, 4.7) | 8.5 (5.6, 12.6) | 19.5 (11.1, 31.0) | - |
Inhibin B/FSH ratio | 21 (10, 42) | 39 (23, 70) | 51 (31, 93) | <0.001 |
LH (U/L) | 4.3 (3.1, 6.0) | 3.9 (3.0, 5.0) | 3.8 (2.8, 5.3) | 0.149 |
Testosterone (nmol/L) | 13 (11, 16) | 14 (11, 18) | 15 (12, 18) | 0.064 |
Testosterone/LH ratio | 3.0 (2.2, 4.5) | 3.6 (2.6, 5.4) | 3.7 (2.8, 5.1) | 0.007 |
Estradiol (pmol/L) | 100 (88, 117) | 97 (86, 112) | 97 (77, 117) | 0.101 |
Testosterone/estradiol ratio | 130 (99, 170) | 148 (115, 184) | 154 (127, 187) | 0.007 |
25OHD (nmol/L) | 50 (30, 61) | 42 (29, 55) | 40 (28, 59) | 0.096 |
Abstinence (days) | 3.6 (3.0, 4.3) | 3.8 (3.0, 4.6) | 3.8 (3.0, 4.6) | 0.516 |
Semen volume (mL) | 3.5 (2.6, 4.5) | 3.8 (2.6, 4.9) | 3.7 (3.0, 4.8) | 0.321 |
Sperm concentration (106/mL) | 7 (2, 23) | 14 (5, 40) | 23 (7, 53) | <0.001 |
Sperm count (106) | 21 (7, 81) | 50 (20, 145) | 76 (25, 192) | <0.001 |
Motile sperm (%) | 39 (23, 53) | 47 (29, 60) | 44 (28, 63) | 0.096 |
Motile sperm (106) | 11 (2, 38) | 27 (7, 76) | 39 (8, 102) | <0.001 |
Progressive motile sperm (%) | 27 (23, 41) | 31 (17, 44) | 31 (16, 52) | 0.114 |
Progressive motile sperm (106) | 6 (1, 25) | 20 (3, 57) | 24 (4, 80) | <0.001 |
Morphological normal sperm (%) | 2.3 (1.0, 5.5) | 2.5 (1.0, 4.8) | 2.5 (1.0, 5.8) | 0.808 |
Morphological normal sperm (106) | 0.5 (0.1, 2.6) | 1.5 (0.2, 4.5) | 1.8 (0.3, 8.1) | 0.006 |
Serum AMH (pmol/L) | Serum inhibin B (pg/mL) | Serum FSH (U/L) | |||||||
---|---|---|---|---|---|---|---|---|---|
β | 95% CI | P | β | 95% CI | P | β | 95% CI | P | |
Sperm concentration (106/mL)a | 1.5% | 0.7–2.4% | < 0.001 | 1.0% | 0.8–1.3% | < 0.001 | −16.2% | −20.3 to −12.0% | < 0.001 |
Sperm count (106)a | 1.6% | 0.8–2.5% | < 0.001 | 1.0% | 0.8–1.3% | < 0.001 | −16.0% | −20.2 to −11.6% | < 0.001 |
Motile sperm (%) | 0.1% | −0.0–0.2% | 0.276 | 0.0% | −0.0–0.1% | 0.294 | −0.6% | −1.2–0.1% | 0.076 |
Motile sperm (106)a | 1.7% | 0.8–2.7% | < 0.001 | 0.9% | 0.6–1.2% | < 0.001 | −15.6% | −20.3 to −10.7% | < 0.001 |
Progressive motile sperm (%) | 0.1% | −0.0–0.2% | 0.152 | 0.0% | −0.0–0.0% | 0.243 | −0.5% | −1.1–0.1% | 0.085 |
Progressive motile sperm (106)a | 1.8% | 0.8–2.7% | < 0.001 | 1.0% | 0.6–1.3% | < 0.001 | −16.1% | −21.0 to −11.0% | < 0.001 |
Morphological normal sperm (%)a | 0.4% | −0.0–0.9% | 0.058 | 0.1% | −0.1–0.2% | 0.301 | −3.0% | −5.9–0.0 % | 0.049 |
Morphological normal sperm (106)a | 2.2% | 1.2–3.3% | < 0.001 | 1.0% | 0.7–1.3% | < 0.001 | −17.6% | −22.6 to −12.4% | < 0.001 |
Low AMH and high FSH (n=49) | Low AMH or high FSH (n=102) | Neither low AMH nor high FSH (n=147) | *P-value | |
---|---|---|---|---|
Age (years) | 38 (34, 42) | 34 (30, 39) | 33 (29, 38) | <0.001 |
BMI (kg/m2) | 26 (23, 29) | 25 (24, 29) | 26 (23, 28) | 0.891 |
Smoking (%) | 21 (%) | 30 (%) | 22 (%) | 0.278 |
Cryptorchidism (%) | 23% | 18% | 11% | 0.070 |
Testis size (mL) | 15 (13, 19) | 18 (15, 21) | 20 (17, 25) | <0.001 |
Testosterone (nmol/L) | 14 (11, 16) | 14 (11, 17) | 14 (11, 17) | 0.603 |
Testosterone/LH ratio | 2.4 (1.6, 3.9) | 3.3 (2.4, 4.4) | 4.0 (2.8, 5.8) | <0.001 |
Estradiol (pmol/L) | 98 (87, 115) | 102 (82, 121) | 97 (83, 113) | 0.441 |
Testosterone/estradiol ratio | 130 (113, 184) | 143 (113, 180) | 149 (120, 186) | 0.265 |
Abstinence (days) | 3.8 (3.3, 4.0) | 3.5 (3.0, 4.3) | 3.8 (3.0, 4.8) | 0.381 |
Semen volume (mL) | 4.0 (2.6, 5.0) | 3.4 (2.6, 4.4) | 3.8 (2.9, 5.0) | 0.066 |
Sperm concentration (106/mL) | 4 (1, 9) | 10 (2, 26) | 23 (8, 55) | <0.001 |
Sperm count (106) | 14 (3, 36) | 39 (8, 85) | 84 (28, 189) | <0.001 |
Motile sperm (%) | 32 (23, 53) | 46 (27, 57) | 47 (29, 64) | 0.042 |
Motile sperm (106) | 6 (1, 17) | 17 (3, 41) | 39 (10, 103) | <0.001 |
Progressive motile sperm (%) | 24 (13, 40) | 32 (13, 44) | 31 (17, 51) | 0.067 |
Progressive motile sperm (106) | 4 (1, 14) | 10 (2, 30) | 24 (4, 80) | <0.001 |
Morphological normal sperm (%) | 2.0 (0.8, 3.8) | 2.1 (1.0, 4.9) | 2.8 (1.4, 6.0) | 0.182 |
Morphological normal sperm (106) | 0.2 (0.1, 1.0) | 0.6 (0.1, 2.9) | 2.1 (0.4, 8.4) | <0.001 |